Translational engagement of lysophosphatidic acid receptor 1 in skin fibrosis: from dermal fibroblasts of patients with scleroderma to tight skin 1 mouse.


Journal

British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536

Informations de publication

Date de publication:
09 2020
Historique:
received: 27 02 2019
revised: 02 03 2020
accepted: 17 06 2020
pubmed: 7 7 2020
medline: 28 5 2021
entrez: 7 7 2020
Statut: ppublish

Résumé

Genetic deletion and pharmacological studies suggest a role for lysophosphatidic acid (LPA Dermal fibroblast and skin biopsies from systemic sclerosis patients were used. Myofibroblast differentiation, gene expression and cytokine secretion were measured following LPA and/or SAR100842 treatment. Pharmacolgical effect of SAR100842 was assessed in the tight skin 1 (Tsk1) mouse model. SAR100842 is equipotent against various LPA isoforms. Dermal fibroblasts and skin biopsies from patients with systemic sclerosis expressed high levels of LPA The effects of SAR100842 on LPA-induced inflammation and on mechanisms linked to fibrosis like myofibroblast differentiation and Wnt pathway activation indicate that LPA

Sections du résumé

BACKGROUND AND PURPOSE
Genetic deletion and pharmacological studies suggest a role for lysophosphatidic acid (LPA
EXPERIMENTAL APPROACH
Dermal fibroblast and skin biopsies from systemic sclerosis patients were used. Myofibroblast differentiation, gene expression and cytokine secretion were measured following LPA and/or SAR100842 treatment. Pharmacolgical effect of SAR100842 was assessed in the tight skin 1 (Tsk1) mouse model.
KEY RESULTS
SAR100842 is equipotent against various LPA isoforms. Dermal fibroblasts and skin biopsies from patients with systemic sclerosis expressed high levels of LPA
CONCLUSION AND IMPLICATIONS
The effects of SAR100842 on LPA-induced inflammation and on mechanisms linked to fibrosis like myofibroblast differentiation and Wnt pathway activation indicate that LPA

Identifiants

pubmed: 32627178
doi: 10.1111/bph.15190
pmc: PMC7443477
doi:

Substances chimiques

Receptors, Lysophosphatidic Acid 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

4296-4309

Subventions

Organisme : Target Bio Science
Organisme : Roche
Organisme : Pfizer
Organisme : Merck Sharp and Dohme
Organisme : Mitsubishi Tanabe Pharma Corporation
Organisme : Medscape
Organisme : medac
Organisme : Eli Lilly and Company
Organisme : Kymera Therapeutics
Organisme : iQvia
Organisme : iQone
Organisme : Italfarmaco
Organisme : Horizon (Curzion) Pharmaceuticals
Organisme : Glenmark Pharmaceuticals
Organisme : Ergonex
Organisme : ChemomAb
Organisme : CSL Behring
Organisme : Drug Development International Ltd
Organisme : Competitive Corpus
Organisme : Catenion
Organisme : Blade Therapeutics
Organisme : Baecon Discovery
Organisme : Amgen
Organisme : Acceleron
Organisme : Actelion Pharmaceuticals
Organisme : AbbVie
Organisme : UCB
Organisme : RedX
Organisme : Novartis
Organisme : Inventiva
Organisme : GlaxoSmithKline
Organisme : Galapagos NV
Organisme : Celgene
Organisme : Boehringer Ingelheim
Organisme : Bayer
Organisme : Bristol-Myers Squibb
Organisme : aTyr
Organisme : ARXX
Organisme : Array BioPharma
Organisme : Active Biotech
Organisme : Anamar
Organisme : Sanofi

Informations de copyright

© 2020 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

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Auteurs

Laetitia Ledein (L)

Cardiovascular & Metabolism Unit, Sanofi, Chilly-Mazarin, France.

Bertrand Léger (B)

Cardiovascular & Metabolism Unit, Sanofi, Chilly-Mazarin, France.

Clara Dees (C)

Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany.

Christian Beyer (C)

Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany.

Alfiya Distler (A)

Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany.

Serena Vettori (S)

Department of Clinical and Experimental Medicine, Rheumatology Unit, Second University of Naples, Naples, Italy.

Rachid Boukaiba (R)

IDD Department, Sanofi, Vitry-sur-Seine, France.

Jean Pierre Bidouard (JP)

Cardiovascular & Metabolism Unit, Sanofi, Chilly-Mazarin, France.

Matthias Schaefer (M)

R&D Diabetes Division, Sanofi, Frankfurt, Germany.

Josef Pernerstorfer (J)

R&D Diabetes Division, Sanofi, Frankfurt, Germany.

Hartmut Ruetten (H)

R&D Diabetes Division, Sanofi, Frankfurt, Germany.

Alexandre Jagerschmidt (A)

Cardiovascular & Metabolism Unit, Sanofi, Chilly-Mazarin, France.

Philip Janiak (P)

Cardiovascular & Metabolism Unit, Sanofi, Chilly-Mazarin, France.

Jörg H W Distler (JHW)

Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany.

Oliver Distler (O)

Department of Rheumatology, University Hospital Zurich, Zürich, Switzerland.

Stéphane Illiano (S)

Cardiovascular & Metabolism Unit, Sanofi, Chilly-Mazarin, France.

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Classifications MeSH